Expectation of abnormality on paternal and maternal sides: a computational model.

Edwards (i960, i963) has recently pointed out that conditions which have been attributed to the effects of a single major gene of diminished penetrance are also capable of being explained as the result of polygenic factors, if the condition in question is not very infrequent. It is only necessary to suppose that polygenic factors bring about a predisposition which expresses itself in a recognizable apparently qualitative deviation, once it has passed a given threshold. There is, for instance, evidence that the presence or absence of the hare-lip/cleft palate syndrome is due to polygenic factors (Carter, i965). It is supposed that there is a critical stage in development by which time the embryonic layers involved must have united; a delay in union short of this point is without effect, but beyond it leaves an incomplete state which is never made good. Edwards has also pointed out that the two alternative hypotheses are very alike in their effects, so that it is difficult to devise tests to distinguish between them. Nevertheless, it is important to make such a distinction if possible, since they are not equivalent. It has been said that the penetrance of every gene is complete, given the right test of its biochemical action. A hypothesis of major gene action, therefore, suggests investigation along biochemical lines. The polygenic hypothesis is of less heuristic value. It occurred to the writer that it should be possible to distinguish between polygenic inheritance and the effects of a single dominant major gene with diminished penetrance, by noting the distribution of secondary cases among the relatives on the paternal and maternal sides of the ascendance of affected individuals. On the single gene hypothesis one would expect, in the cases where two or more affected relatives were known, that these would be either on the patemal or the matemal side, but not